Peripheral vascular disease can result in a number of serious infections complicating ischemia. However, infections as primary causes of peripheral vascular disease, although uncommon, are also very important clinically. Overall, the arterial vascular system is relatively resistant to infection, but infections do occur, often with terrible consequences. Although uncommon, arterial infections can be seen with a variety of microbial pathogens. Pyogenic bacterial infections are most frequently recognized, but infections with atypical bacterial pathogens, spirochetes, mycobacteria, fungi, parasites, helminths, and even viruses also occur. Diagnosis can be extremely difficult, and many times the infection is not diagnosed until the time of vascular surgery for arterial rupture or another catastrophic event, or at autopsy. Therapy can be just as challenging. Even with a combined medical and surgical approach, arterial infections can be very difficult to eradicate. These infections are associated with significant morbidity and mortality, even if microbiological cure can be achieved.
Not all the effects of infection on peripheral arteries are direct. In some cases, the infection incites a vasculitis. It is the resulting inflammation, with or without ongoing arterial infection, that leads to arterial disease. Finally, direct infection and indirect effects of chronic infections on the arterial system may be subclinical, but these asymptomatic infections may cause endothelial cell dysfunction or lead to pathologic changes, including accelerated atherosclerosis.
Peripheral arterial infections have been comprehensively reviewed in a number of books, chapters, and other reviews.1,2 This chapter will attempt to review the subject with inclusion of new information and a discussion of contemporary management issues and controversies, as well as discuss the entire breadth of infectious agents that can directly or indirectly affect the peripheral vascular system.
NATURALLY OCCURRING BACTERIAL AND FUNGAL INFECTIONS OF THE ARTERIAL VASCULATURE, I.E., INFECTIOUS ARTERITIS
Although the term mycotic aneurysm is often used for any arterial infection, other terminology may be used that gives some insight into the pathogenesis. Wilson et al.3 devised a commonly used classification of arterial infections: Mycotic aneurysms caused by septic embolization from endocarditis, secondarily infected atherosclerotic aneurysms, infectious arteritis without aneurysm formation or necrotizing arteritis, and finally infected pseudoaneurysms from trauma or a vascular procedure. Even this classification is not all encompassing, and does not include arterial infections caused by local spread from an adjacent site of infection.
Infections of the arterial system are relatively rare. In general, the ability of bacteria to bind and cause infection of the arterial endothelial surface is low, but the exact incidence of infectious arteritis is not well defined. Even autopsy data on the frequency of this type of infection is limited, and usually reports only focus on very large vessels, such as the aorta or, in some studies, the femoral arteries. Furthermore, many of the large autopsy studies that reference infectious arteritis were done decades ago, and the relative incidence of different types of arterial infections has dramatically changed over time. However, these earlier studies do highlight the rarity of these infections. For example, the frequency of aneurysms of the aorta in a frequently referenced autopsy study at the Boston City Hospital from 1902 to 1951 was very low, 1.5%, and only 2.6% of these were infectious.4 The presence of an atherosclerotic plaque or aneurysm predisposes a patient to this type of infection, and this is the reason for the historic male predominance and older age, usually more than 65 years. The reported incidence of infected aneurysms at other sites, such as the iliac arteries, is also low. Data from examination of pathology samples indicate that abdominal aortic aneurysms may be infected relatively frequently compared to other arterial structures, but the majority of patients have no constitutional symptoms, signs, or laboratory evidence of infection premortem. Some studies have shown a high incidence of positive arterial cultures, even in cases of clean elective vascular repair.5 This may indicate that the infection is very well localized or is just a bystander infection, but if a repair is performed in-situ, these infections can certainly have importance.6 If these infections are not diagnosed until surgery is performed, then there is the risk of recurrent infection, especially if there has been a repair using a prosthetic device. Conversely, if a patient has fever, there is at least a clue that may indicate the presence of infection and allow diagnosis prior to local arterial complications such as rupture.
In the preantibiotic era, the vast majority of clinically apparent mycotic aneurysms were caused by septic embolization in patients with bacterial endocarditis.3 Antibiotic therapy for endocarditis has greatly reduced the incidence of arterial infection. As the frequency of mycotic aneurysms from endocarditis has decreased, the proportion of infectious arteritis cases caused by seeding of an atherosclerotic aneurysm or plaque has increased, at least in the United States. Infectious arteritis is rare in childhood, except in the case of mycotic aneurysms from infective endocarditis or congenital cardiovascular malformations, such as coarctation of the aorta. Both the mode of arterial infection and the etiologic agent can vary geographically, and is quite different in the tropics as compared to developed countries. For example, cerebrovascular disease in the tropics may be attributable to one of a multitude of infectious etiologic agents, including cysticercosis, infective endocarditis, Chaga’s disease, viral hemorrhagic fevers, gnathosomiasis, leptospirosis, cerebral malaria, and tuberculosis (TB)—infections that would for the most part be extremely unlikely in the United States.7
Several routes of infection have been recognized in the pathogenesis of infections of the peripheral arterial system. Infections of the arterial vasculature can result from septic embolization from the heart, seeding from bacteremia or fungemia, or local invasion from an adjacent infectious process. Penetrating injuries, accidental or related to drug use, or related to invasive medical procedures involving arteries, are another route of local invasion. The relative importance of each of these modes of infection has changed since the advent of antibiotic therapy.
Mycotic aneurysm is the term most often used for local arterial infection caused by septic embolization. Although mycotic is an adjective usually reserved for fungal infections, this term has now been adopted for local arteritis from embolization as a result of all types of pathogens, even when there is no actual dilation of the involved vessel. Mycotic aneurysms from septic embolization most often occur from occlusion of the lumen of a vessel, usually at the vessel’s bifurcation, with a large and infected embolus. Small micromboli can also go the vaso vasorum of larger arteries, also leading to the formation of mycotic aneursysms. As already stated, mycotic aneurysms from embolization occur most frequently in patients with endocarditis. Although this complication is much less frequent today than in the antibiotic era, it is still associated with significant morbidity and mortality. In a recent study of patients with endocarditis, 18% developed mycotic aneurysms, and the morbidity and mortality from rupture was significant.8 Most of the mycotic aneurysms complicating endocarditis involve the sinuses of Valsalva or the most proximal ascending aorta just above the heart valves. Less often, major intracranial, peripheral, and visceral arteries are involved. One of the most serious complications of septic embolization in infective endocarditis is cerebral artery embolization. When this occurs, the mortality rate from endocarditis greatly increases. Even if the patient survives the stroke, the risk of subsequent rupture remains. Anticoagulation, which is often necessary in patients who have required valve replacement after an episode of endocarditis, results in extremely high mortality if bleeding occurs. Although rupture and bleeding of mycotic aneurysms is usually caused by dilation and thinning of the vessel wall, bleeding from non-dilated infected vessels termed septic necrotic arteritis, can also occur.
Visceral aneruysms are extremely rare, but are caused by either infective endocarditis or polyarteritis nodosa (PAN). These may involve the superior mesenteric artery, celiac artery, or hepatic artery, resulting in ischemia of visceral organs. Involvement of other visceral arteries is less common.
Cerebral infarction caused by infectious endarteritis can also be a complication of severe bacteremic infections other than endocarditis, including common infections such as community-acquired bacterial pneumonia. Septic emboli from non-cardiac sources, arteritis as a result of seeding during high grade bacteremia, and/or activation of the coagulation system can all result in cerebral infarction from infectious endarteritis.9
Mycotic anerusysms or necrotizing arteritis from seeding of an atherosclerotic vessel is found most often in the abdominal aorta. 70% of the time the ascending thoracic aorta is involved, and 15% of the time the descending thoracic aorta is involved. Infected aneurysms usually show neutrophilic infiltration, necrosis, abscess formation, and hemorrhage. Thoracic or lumbar vertebral osteomyelitis can sometimes be found. The contiguous spread may be in either direction, from the osteomyelitis to the aorta or from the aorta to the bone.
Although atherosclerosis is the most common pre- existing arterial abnormality, other arterial diseases such as medial necrosis and vasculitis can also predispose a patient to arterial infection. Any organism causing transient bacteremia could do this, including transient bacteremia complicating invasive procedures. Infectious endarteritis in the absence of an aneurysm or preexisting atherosclerotic disease may occur, but this is extremely rare and often not identified premortem.
Local infection can result in arterial infection through direct extension. For example, cerebral arteritis and aneurysm formation may also complicate acute bacterial meningitis.10 Cerebral artery angiitis from an adjacent subdural empyema has also been reported.11 Carotid artery occlusion resulting in a stoke syndrome has occurred as a consequence of necrotizing fasciitis of the lateral neck space.12 Actinomycosis has caused a severe vasculitis in arteries in the basilar meningeal region caused by direct intracranial spread from a local head and neck infection.13 Arterial infection can also complicate sinusitis, complicated skin and soft tissue infections, vertebral osteomyelitis caused by pyogenic bacteria or tuberculosis, or any local infection with adjacent spread.
Any accidental trauma can result in an arterial infection, particularly if there is significant arterial damage, as is often seen with gun shot wounds and motor vehicle accidents.14 This usually involves the extremities and in most cases, there is pseudoaneurysm formation. Injection drug use is one nonaccidental, nonmedical procedure that can cause arterial trauma and arterial infection. The incidence of infections of peripheral arteries caused by injection drug use is lower than one might expect, only 0.03% in one study.15 When these infections do occur, they can be any artery that is injected, including the brachial, radial, carotid, femoral, or other lower extremity arteries. There is often an associated subcutaneous abscess or musculoskeletal infection such as septic arthritis.
Given the relatively low rates of infections complicating injection drug use, it is not surprising that invasive procedures performed using standard sterile procedures are infrequently associated with arterial infection. Despite low rates, however, these infections occur in ever-increasing numbers because of the vast numbers of procedures performed, including vascular surgery, cardiac catheterization, angioplasty, stent placement, arterial chemotherapy catheters, and radial artery catheters for monitoring.
Even a one-time puncture of an artery for a procedure, or even an arterial puncture to obtain a blood gas specimen, can result in inoculation and infection or intimal damage and subsequent seeding of the artery from transient bacteremia or fungemia. Although infection would be expected at the site of the arterial puncture, infection of an external iliac artery has occurred a distance from the insertion site, presumably from trauma caused by the tip of the catheter.16 Infection of percutaneous suture closure devices can occur after catheter-based interventions. Infection is rare with only six infections in 822 cases (0.7%) in one study.17 Resolution requires exploration, removal of the suture closure device, and in most cases, autologus repair. In some cases, even more extensive surgical management is needed for complications from these devices.18
Some arterial manipulations are performed early in life, and newborn infants undergoing umbilical artery catheterization may develop staphylococcal mycotic aneurysms affecting the aorta, femoral arteries, or multiple sites.19 Radial artery infections secondary to arterial lines are rare, but have serious complications. The incidence is only 0.2%, but bacteremia, radial artery mycotic aneurysms, and secondary sternal wound infections may occur.20
Arterial surgery can also lead to arterial infections, even without grafting. When arteritis complicates cardiac surgery, the results are often disastrous. The organisms most often involved are common nosocomial pathogens associated with wound infections, but more unusual organisms may be seen in immunocompromised hosts. A number of cases have resulted from Listeria, most often in the very young, very old, or immunosuppressed.21 Candida spp. may also be involved, and interestingly has been seen in many renal transplant patients, with infection of the vascular pedicle. In one case, this pathogen was most likely carried over from the donor, as it was found in the conservation fluid from the graft.22 Renal artery mycotic aneurysms in general are a particular problem for renal transplant recipients. A postoperative peripnephric infection can result in infection at the arterial anastomosis.23 Candida infection of the graft used to vascularize the pancreas graft was seen in two recipients of pancreas–kidney transplants. This led to the loss of both pancreatic grafts.24
Infected stents may lead to arterial infection, and this has resulted in subclavian arteritis and pseudoaneurysm formation.25 Rupture of the iliac artery and anursysmal transformation of the abdominal aorta has been reported with infection of metallic iliac artery stent placement.26 Renal artery stents have also become infected.27
Epidemiology. Prosthetic vascular grafts are even more susceptible to infection, and the rates vary between 1% and 6% depending on many factors.28,29 Emergency surgery, reoperation, and diabetes are major risk factors. The site of the graft also contributes to the risk of infection, with lower rates for aortic grafts, intermediate rates for aortofemoral grafts, and the highest rates for femoro-popliteal grafts. All are associated with significant mortality, 17% to 24%, and an even higher rate of morbidity, usually limb amputation.30
Pathogenesis. Just as native arteries can be infected by a number of routes, prosthetic vascular grafts can also be infected by several routes. The grafts may be infected at the time of placement or after subsequent manipulations, including repair. Infection can also spread from a local area of infection or colonization, including the surgical wound. Other local infections, including cellulitis or other skin and soft tissue infections can lead to graft infection. Grafts can also be infected hematogenously. The risk of hematogenous seeding is greatest early after implantation, when the graft has not been endothelialized, but never disappears because graft coverage is never complete. Although early graft infection can occur, most infections present after many months.
The microbiology of arterial infections is quite varied. In mycotic aneurysms from septic embolization, the microbial etiology mirrors that of endocarditis, and all the organisms that are recognized as principal endocarditis agents may be involved. The agents listed in the revised Duke criteria for endocarditis include Staphylococcus aureus, viridans streptococci, Enterococci, Streptococcus bovis, and HACEK organisms (Hemophilus spp., Actinobacillus, Cardiobacterium, Eikenella, and Kingella, all gram-negative coccobacilli) are the usual culprits. These organisms are readily isolated from the blood in most circumstances.
In the preantibiotic era, infectious arteritis caused by bacteremia complicating common pyogenic infections involved pneumococcus, group A streptococcus, and gonococcus. These agents also commonly caused endocarditis in that era. In many instances, no underlying arterial disease was known to preexist. These infections are now rare, as are the cases of endocarditis caused by these agents, but some organisms can still infect normal arteries. Meningococcus frequently infects the walls of arteries, resulting in obstruction and infarction of the skin, and is one of the causes of purpura fulminans. Visceral organs such as the adrenals may also infarct from vascular occlusion. In one study,31 20 patients with peripheral arteritis presumed as a result of infection were studied to find out the etiology. Ten patients had meningococcal disease. Meningococci were found in the vessel walls of ischemic areas. Other patients did not have organisms in the vessel wall, but had vasculitis following streptococcal infection and measles, and these patients seemed to respond to anticoagulation with heparin. Pseudomonas aeruginosa can cause severe vascular disease and vascular occlusion in patients with neutropenia.32 The characteristic necrotic lesions of ecthyma gangrenosum result from occlusion of cutaneous vessels by the organisms themselves.
Many bacterial pathogens can infect an atherosclerotic plaque or aneurysm. Gram-positives, S. aureus, different coagulase-negative staphylococcal species, viridans streptocooci, and enterococci predominate, but a variety of enteric gram-negative rods have been implicated. Listeria monocytogenes is an uncommon cause of arterial infection but can occur in aneurysms of previously operated arteries in very young, very old, or immunocompromised patients.21 Several anaerobes have also been involved. Clostridium septicum can cause aortitis in patients with an underlying gastrointestinal (GI) or hematologic malignancy, with mortality approaching 70%.33 Although many organisms can cause arterial infection, certain organisms are preferentially associated with this type of infection. Although arterial infection with Salmonella is rare, it remains one of the most common causes of primary mycotic aneursysm.34,35 Overall, Salmonella spp. are involved in up to 20% of the cases. Although bacteremias can occur from gastroenteritis with any species of Salmonella, when patients are older than 50 years of age, bacteremia is associated with an intravascular focus in up to 25% of cases. Forty percent of the Salmonella isolates are Salmonella enteritidis strains, which is similar to the proportion of cases causing gastroenteritis. Not all cases result from enteric infection, and Salmonella bacteremia can also complicate urinary tract infections with these species.36 Other species, however, have an even greater propensity for vascular infection. Salmonella choleraesuis, the best example, may be involved in 30% of cases of aneurysms infected with Salmonella, a much higher percent than that for enteritis caused by this organism.37 A retrospective study showed a gradual increase in bacteremia caused by Salmonella from 11 cases in 1984 to 58 cases in 1988.38 Arizona spp. are closely related to Salmonella, and they have also been involved in aortic infection complicating atherosclerosis.39
Certain bacteria are not seen in cases of infectious arteritis in the United States, but have been implicated in endemic areas. Burkhoderia pseudomallei bacterial arteritits occurs in endemic areas in Southeast Asia.40
Syphillis can cause an arteritis. Classically this is an ascending aortitis in patients with longstanding infection. Syphilis can also cause central nervous system (CNS) disease resulting from an arteritis that can be demonstrated by conventional angiography or MRA.41 Although this can occur in anyone with tertiary syphilis, it is more common in human immunodeficiency virus (HIV)-infected patients. Labauge et al.42 reported on a HIV-infected patient with infarction of the pons caused by neurosyphilis. After the patient developed right hemiparesis, he recovered after two courses of IV penicillin.42 Syphilis can also cause areas of vasculitis and obliterative arteritis in the placenta as a result of maternal infection.43 Sometimes a spirochetal infection can mimic a non-infectious vasculitis.44 A 71-year-old male developed vision loss and headache. Temporal artery biopsy showed giant cell arteritis (GCA), but corticosteroid therapy failed. A blood culture later grew spirochetes. The patient was subsequently treated with ceftriaxone and regained some sight. Leptospirosis can also be associated with cerebrovascular disease. Twelve cases caused by Leptospirosis pomona have been characterized, with cerebral panarteritis and infarctions.45
Fungi are much less common agents of mycotic aneurysms and septic arteritis, except in the chest. When infection with fungi occur, most are caused by Candida or certain molds, particularly Aspergillus and the agents of mucormycosis. These infections usually affect immunocompromised patients or result from nosocomial complications. A renal transplant patient developed a painless groin mass caused by a common femoral artery pseudoaneurysm and saccular aneurysm of the infrarenal aorta due to Candida that occurred a few weeks after a colonoscopy.46 An infected abdominal aortic aneurysm occurred after a nosocomial catheter-related candidemia. These incidence of such secondary fungal infections may start to increase as the incidence of nosocomial fungemia increases.47
Aspergillus spp. and the zygomycetes, the agents of mucormycosis, have a propensity to invade blood vessels. This occurs most frequently with infections in the chest or sinuses.48 Infection can spread from the sinuses to the orbital and CNS, and it may be the subsequent cerebrovascular involvement that predominates.49,50 This may result in confusion with another non-infectious condition, and a case of orbital aspergillosis mimicking temporal arteritis (TA) has been described.50 These species can also cause fungal arteritis with vascular occlusion at operative sites.49,51,52,53, Intracranial aneurysms caused by Aspergillus have a tendency to rupture and bleed.54,55
The endemic fungi, such as histoplasmosis and coccidioidomycosis, may rarely cause vascular disease.56 However, one fungal pathogen can cause a vasculitis, usually in the lower extremities, as a result of soft tissue infection. Pythium insidiosum, is the agent of pythiosis, a life-threatening infection of both humans and animals.57,58 This infection is endemic in Thailand and presents as keratitis or arteritis. There can be vascular occlusion of the large vessels of the lower extremities caused by ascending artertis, often in patients with thalessemia or in patients on chelation therapy with deferoxamine. Infection may also be an occupational disease, as most of the affected individuals have been farmers. This serous infection often leads to limb amputation.59
The usual mycotic aneurysm from Mycobacterium tuberculosis is a pulmonary artery aneurysm from a cavitary lung infection. This is the classic Rasmussen’s aneurysm, which can rupture and lead to death due to massive hemoptysis. Infection of peripheral arteries is much less frequently recognized. Bacteremia and dissemination occurs frequently in tuberculosis, but this is often asymptomatic and subclinical except in patients with the syndrome of miliary TB. Although arterial involvement can be a part of disseminated disease, this is extremely rare. More frequent is involvement of the aorta and formation of a mycotic aneruysm caused by reactivation from a granuloma in close proximity.
Arteritis from parasitic diseases is very uncommon and varies according to geographic location. In the United States, cysticercosis occurs fairly frequently, usually in immigrants or in those with a history of travel to endemic areas. Cerebral arteritis can occur with subarachnoid cysticercosis. This can be seen on angiography even in the absence of clinical symptoms. Most cases involve the middle and posterior cerebral arteries. When symptoms do occur, stroke is the most common syndrome.60 Another infection seen in the United States is strongyloidasis. Patients with immune deficiencies can develop a hyperinfection syndrome from this usually less severe intestinal infection. One case report describes a patient with strongyloides hyperinfection and related E. coli sepsis, who also developed mesenteric thrombosis. The occluded vessel contained numerous filiform larvae.61 In other countries, helminths may cause vascular occlusion in affected individuals.62
The aneurysms and arteritis associated with injection drug use are usually caused by S. aureus and P. aeruginosa, but other pathogens have been reported. Arterial infections caused by invasive arterial procedures and vascular surgery are similar to those seen in other nosocomial infections. Most are common noscomial bacterial pathogens. Nosocomial fungal pathogens, Candida and Aspergillus, and rapid-growing mycobacteria that can be involved in surgical infections, can also occur. Although unusual, endemic fungi and even M. tuberculosis have been involved in prosthetic vascular graft infections.63,64
Up to this point, the discussion has focused on macroscopic arteritis, but small arterial vessels may also be the target of infection. Lacunar infarcts in the CNS caused by small vessel disease can result from a number of etiologies. Infection with syphilis, cysticercosis, Helicobacter pylori, HIV, and other viruses have all been implicated.65
When arterial infections occur as a consequence of septic embolization, usually there is other evidence of the underlying infectious disease, such as endocarditis, in the majority of patients. However, complications from the septic embolization, including mycotic aneurysm, may be the clinical reason that a patient will present. Small intracranial mycotic aneurysms are often clinically silent, but patients will develop heachache and rapid alterations in the level of consciousness when hemorrhage or rupture occurs. Larger emboli may cause a stroke. This occurs in up to 21% of cases of infective endocarditis.66 Focal neurologic deficits or seizures may occur first, allowing for imaging and diagnosis prior to rupture and bleeding. Rupture occurs anywhere from 0 to 35 days or longer after the initial diagnosis of infective endocarditis.
Clinical diagnosis of primary arterial infection is often difficult, and patients, unfortunately, may have symptoms for months before a diagnosis is made. Primary bacterial infections of the aorta are particularly difficult to diagnose. The diagnosis should be considered in the setting of fever of uncertain origin combined with pain in the abdomen or back, all fairly nonspecific findings.67 Fever is not a universal finding by any means and is absent in up to 30% of cases. The nonspecific nature of many of the clinical symptoms and signs, however, results in late diagnosis, often after rupture of the anerusym in approximately 70% of the cases. Rupture can occur with bleeding into the peritoneal cavity, retroperitoneum, pleural cavity, or mediastinum. Rupture may even occur in the absence of aneurysm formation.68 Sometimes, an aortoenteric fistula, usually between the aorta and the third portion of the duodenum, will present with upper GI bleeding. Less frequent signs are an abdominal mass, ureteral obstruction caused by mass effect, or lower GI bleeding. Aneurysms of the iliac or femoral artery result in leg pain. When more peripheral arteries are involved, a painful swelling may be present as a result of a mycotic aneurysm or pseudoaneurysm. A pulsatile mass due to hematoma from hemorrhage may occur, without true dilation of the lumen.69 A draining sinus is rare, but is very indicative of infective. A patient with continuing primary bacteremia (despite appropriate antibiotic therapy in patients without endocarditis on echocardiography) should be suspected of having an infected aneurysm.
The clinical presentation of arterial infections from instrumentation or involving a prosthetic graft is similar to that of primary arterial infection.70 Patients with an aortofemoral graft infection often present with a painful mass in the groin, with or without fever. Patients with more peripheral graft infection usually have fever and a purulent wound infection. Pseudoaneruysms will form at anastomotic sites. Distal septic emboli and graft occlusion may also occur. Pateints who develop an aortoenteric fistula between the graft and small bowel may present with GI bleeding.
There are no definitive routine laboratory tests that can be performed to make this diagnosis. Leukocytosis and elevations of acute phase reactants are frequent, but nonspecific. Microbiologic investigations are obviously necessary to determine the infectious etiology. Bacteremia is common, but the proportion of patients with positive blood cultures varies according to the type of aneurysm or arteritis, even though all these infections are intravascular and continuous bacteremia with multiple positive blood cultures over time would be expected. Blood cultures are positive in approximately 90% of the cases of aneurysms complicating infective endocarditis, while atherosclerotic anerusyms that are infected are associated with positive blood cultures in only 50% of cases. Fungal pathogens, most often Candida spp., can be isolated from blood, but others, such as Aspergillus spp., are almost never isolated from blood (Figure 11-1). Cultures of perigraft fluid can be helpful when obtained, but this requires a clinical suspicion and imaging of the involved vessel. In cases of arterial occlusion from an embolus that is managed by thrombectomy, the removed clot should be sent for smears, cultures, and histopathology. If infection is suspected and the patient undergoes surgery, it is extremely important to perform microbiologic evaluation of samples taken, in particular of the involved portion of the vessel that may be removed.
FIGURE 11-1.
Microbiologic smears in the diagnosis of arterial infections. (A) A periodic-acid Schiff (PAS) stain demonstrating the pseudohyphae of a Candida spp. in the infected clot from a prosthetic arteriovenous fistula for hemodialysis. This confirmed that the graft was the source of candidemia in this patient. (B) A Gomori methenamine silver (GMS) stain demonstrating the uniform width, septate hyphae branching at 45-degree angles, which is characteristic of invasive aspergillosis. The hyphae are seen in a clot in the renal artery that extended from a prosthetic aortic graft. Blood cultures were negative, and the microbiologic studies of the material from the clot were the only specimens that identified the etiologic agent.
Many of the pathogens previously discussed do not readily grow in culture. They may be seen on pathologic examination, but other testing can be useful in the preoperative diagnosis. For example, serologic testing for syphilis is quite sensitive and specific.
Radiographic imaging is usually required to document or confirm the clinical diagnosis of an arterial infection (Figure 11-2). Plain films have rarely shown gas in the surrounding tissues with arterial infection, but in general are of little help. Aortic infections may be well demonstrated by helical CT.71 For other vessels, particularly the cerebrovasculature, arteriography still remains the reference examination for stenosing arteriopathies.72 MRA can show small aneurysms, 2 to 3 mm in diameter. False tests can occur, and nothing performs better than the four-vessel cerebral angiography. It is generally the best test for demonstrating other vascular pathology, pseudoaneurysm and the extent of vascular occlusion. Although CT imaging is often helpful, it may not be sensitive enough to show the aneurysmal dilatation of the involved vessel. Abdominal aortic aneurysms that have no calcification should be considered to be infected, since calcification is very common in bland atherosclerotic aneurysms. Ultrasound can show fluid collections around infected arteries and prosthetic vascular grafts, but it is difficult to determine a perigraft fluid collection is infected in the early postoperative periods, is due to infection or simply post-operative inflammation. Perianeurysmal fluid collections are another sign of infection, and a potential source of culture material. Echocardiographic findings are major criteria for the diagnosis of endocarditis, but can also be useful in detecting mycotic aneurysms in the ascending aorta.
FIGURE 11-2.
Computed tomography (CT) in the diagnosis of an aortic mycotic aneurysm. The study shows a saccular aneurysm of the aorta at the level of the renal arteries. There is a large hematoma surrounding the aneurysm with extension into the retroperitoneum, indicating rupture of the aneurysm. Cultures from surgery grew Streptococcus pneumoniae.
Labeled white cell studies also have a role in the diagnosis of vascular graft infections, but false-negative tests occur (Figure 11-3). Williamson et al. performed 30 Indium-111-labeled white blood cells scan in 21 patients with suspected vascular graft infections and compared the results to CT73. The scans were 100% sensitive in identifying all grafts found to be infected at surgery. Indium scanning was found to be 88% specific; there was 15 true negatives and 2 false positives. CT was less sensitive (37%) when the criteria of fluid and/or gas surrounding the fluid was used as an indicator of infection. The labeled white cell scans also identified extragraft infections. The usefulness of white cell scans has been shown in other studies as well, but false-positive tests have been seen in the first 4 weeks after graft implantation, and antibiotic therapy prior to the examination can decrease sensitivity.74 Tc-99m-labled antigranulocyte antibodies (LeukoScan) are also being evaluated for detection of infection in different clinical settings, but specific data on vascular infections, although favorable, are limited.75
FIGURE 11-3.
Labeled white cell scanning in the radiographic evaluation of a mycotic aneurysm. (A) CT of the aorta with thrombosis of an aortic graft below the renal arteries. There is a gas/fluid level in the lumen. (B) Image from an Indium-labeled white cell scan after 6 weeks of intravenous, combination antibiotic therapy. There was still uptake in the same vicinity indicating persistent infection and resection of the involved graft was required for cure.
In those patients who develop GI bleeding as a consequence of an aortoenteric fistula, endoscopy may help with diagnosis, but this manifestation is very unusual.
Despite comprehensive reviews of this topic, it is hard to be adamant about the management of arterial infections, since none of the approaches have been proven in controlled trials.76,77 Management includes antimicrobial therapy with or without surgery, and the surgical approach can be debated. Often there will have to be a personalized treatment plan. The management of graft infections is particularly difficult, and the British Society for Antimicrobial Chemotherapy has set up a multidisciplinary working group to come up with a consensus statement that will make recommendations regarding diagnosis and therapy.78 Some general principles, many shared with other types of prosthetic infections, can be followed.79
The antimicrobial therapy is probably most agreed upon course of action, with prolonged courses of intravenous antibiotics typically being recommended. In certain situations, such as cerebral artery mycotic aneurysms complicating septic embolization from infectious endocarditis, surgery is not a feasible option. Effective antimicrobial therapy alone, however, may result in reduction in size and complete resolution is not uncommon. Serial angiographic studies or other imaging may be useful in following mycotic aneurysms when a more expectant approach is taken.80 In one series reported by Kovoor et al.,81 complete resolution occurred in two-thirds of patients who were managed with antibiotics alone and repeat angiography. Mycotic aneurysms complicating septic embolization from infectious endocarditis are treated like endocarditis, with prolonged courses of parenteral, bactericidal antibiotics. Antibiotic therapy should be given for 4 to 6 weeks similar to the course recommended for infective endocarditis. In the case of device-related infections, prolonged courses of oral antibiotics have been used after a course of IV therapy when the device cannot be completely removed or in situ graft replacement has been performed (see below). Even chronic suppressive therapy has been recommended in certain situations where device removal is contraindicated, and observational studies indicate this can be effective and safe.82
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